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Dendritic cell-derived exosomes elicit tumor regression in autochthonous hepatocellular carcinoma mouse models

Lu, Zhen, Zuo, Bingfeng, Jing, Renwei, Gao, Xianjun, Rao, Quan, Liu, Zhili, Qi, Han, Guo, Hongxing, Yin, HaiFang·2017·Journal of Hepatology
DOI 10.1016/j.jhep.2017.05.019
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Abstract

Background & aims Dendritic cell (DC)-derived exosomes (DEXs) form a new class of vaccines for cancer immunotherapy. However, their potency in hepatocellular carcinoma (HCC), a life-threatening malignancy with limited treatment options in the clinic that responds poorly to immunotherapy, remains to be investigated. Methods Exosomes derived from α-fetoprotein (AFP)-expressing DCs (DEX AFP ) were investigated in three different HCC mouse models systemically. Tumor growth and microenvironment were monitored. Results DEX AFP elicited strong antigen-specific immune responses and resulted in significant tumor growth retardation and prolonged survival rates in mice with ectopic, orthotopic and carcinogen-induced HCC tumors that displayed antigenic and pathological heterogeneity. The tumor microenvironment was improved in DEX AFP -treated HCC mice, demonstrated by significantly more γ-interferon (IFN-γ)-expressing CD8 + T lymphocytes, elevated levels of IFN-γ and interleukin-2, and fewer CD25 + Foxp3 + regulatory T (Treg) cells and decreased levels of interleukin-10 and transforming growth factor-β in tumor sites. Lack of efficacy in athymic nude mice and CD8 + T cell-depleted mice showed that T cells contribute to DEX AFP -mediated antitumor function. Dynamic examination of the antitumor efficacy and the immune microenvironment in DEX AFP -treated orthotopic HCC mice at different time-points revealed a positive correlation between tumor suppression and immune microenvironment. Concl…

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Metadata

Authors
Lu, Z., Zuo, B., Jing, R., Gao, X., Rao, Q., Liu, Z., Qi, H., Guo, H., & Yin, H.
Venue
Journal of Hepatology
Publisher
Elsevier BV
Published
2017-10
Volume
67
Issue
4
Pages
739-748
ISSN
0168-8278
DOI
10.1016/j.jhep.2017.05.019
Cited by
361
References
0
Language
en
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)

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CoChat. (2026). Citation check: Dendritic cell-derived exosomes elicit tumor regression in autochthonous hepatocellular carcinoma mouse models. https://app.cochat.ai/papers/10.1016/j.jhep.2017.05.019
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Lu, Z., Zuo, B., Jing, R., Gao, X., Rao, Q., Liu, Z., Qi, H., Guo, H., & Yin, H. (2017). Dendritic cell-derived exosomes elicit tumor regression in autochthonous hepatocellular carcinoma mouse models. Journal of Hepatology. https://doi.org/10.1016/j.jhep.2017.05.019